Hypoxia impairs anti-viral activity of natural killer (NK) cells but has little effect on anti-fibrotic NK cell functions in hepatitis C virus infection.

Background & Aims: Natural killer (NK) cells have been shown to exert anti-viral as well as anti-fibrotic functions in hepatitis C virus (HCV) infection. Previous studies, however, analyzed NK cell functions exclusively under atmospheric oxygen conditions despite the fact that the liver microenvironment is hypoxic. Here, we analyzed the effects of low oxygen tension on anti-viral and anti-fibrotic NK cell activity.

Etiology and Complications of Portal Vein Thrombosis.

Background: Portal venous occlusion represents a disorder with considerable clinical relevance. The underlying causes of portal vein thrombosis (PVT) are frequently multifactorial and include malignancies, progressive chronic liver diseases, processes localized to the epigastrium and hepatobiliary system, and acquired as well as inherited thrombophilia. The three main categorical groups are malignant thrombosis, cirrhotic PVT, and non-malignant, non-cirrhotic PVT.

Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis.

Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation and fibrosis, which might progress to cirrhosis. Human NASH is associated with metabolic syndrome (MS). Currently, rodent NASH models either lack significant fibrosis or MS.

Chemokine (C-X-C motif) ligand 11 levels predict survival in cirrhotic patients with transjugular intrahepatic portosystemic shunt.

Background & Aims: Chemokines, such as CXCR3-ligands, have been identified to play an important role during hepatic injury, inflammation and fibrosis. While CXCL9 is associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL11 in severe portal hypertension remains unknown.

Methods: CXCL11-levels were measured in 136 patients with liver diseases, and 63 healthy controls.

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.

Background And Aims: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data.

The ratio of calprotectin to total protein as a diagnostic and prognostic marker for spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites.

Background: Diagnosis of spontaneous bacterial peritonitis (SBP) is based on a differential ascites leukocyte count which does not provide prognostic information. We performed a pilot study to assess calprotectin in ascites as an alternative diagnostic and prognostic marker.

Methods: We collected ascites from patients with liver cirrhosis from March 2012 to July 2013.

Pulmonary hypertension in HIV infection: a prospective echocardiographic study.

Objectives: While idiopathic pulmonary arterial hypertension (PAH) is a rare disease, it is seen more frequently in patients with HIV infection. The aim of this study was to evaluate the prevalence of pulmonary hypertension (PH) in patients with HIV infection by echocardiographic screening.

Methods: Echocardiography and N-terminal of the prohormone brain natriuretic peptide measurement were used to examine the prevalence of PH prospectively in HIV-positive patients (n = 374) during routine follow-up visits for HIV disease.

Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.

Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia-induced pancreatitis (HTGP). The rationale behind this approach is the depletion of triglycerides and the reduction of inflammatory cytokines. The time span between onset of clinical symptoms and start of plasmapheresis might have an important impact on mortality.

Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver.

Spontaneous bacterial peritonitis (SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP.

Long-term outcome of liver transplant patients with Budd-Chiari syndrome secondary to myeloproliferative neoplasms.

Background: A considerable proportion of patients receiving liver transplants for Budd-Chiari syndrome (BCS) suffer from myeloproliferative neoplasms (MPN). This study evaluated the long-term prognosis of liver-transplanted patients with BCS secondary to MPN and the effect of immunosuppression on MPN progression.

Methods: A total of 78 patients with BCS were evaluated between 1982 and 2013.

Circulating miRNA-122 levels are associated with hepatic necroinflammation and portal hypertension in HIV/HCV coinfection.

Background: Introduction of combined antiretroviral therapy (cART) has improved survival of HIV infected individuals, while the relative contribution of liver-related mortality increased. Especially in HIV/HCV-coinfected patients hepatic fibrosis and portal hypertension represent the main causes of liver-related morbidity and mortality. Circulating miRNA-122 levels are elevated in HIV patients and have been shown to correlate with severity of liver injury.

A pocket guide to identify patients at risk for chronic kidney disease after liver transplantation.

Chronic kidney disease (CKD) after liver transplantation (LT) has a strong impact on transplant and patient survival. After LT, a significant proportion of patients develop renal dysfunction with a high risk to progress to end-stage renal disease (ESRD). Because of the multifactorial nature of CKD in the post-transplant period, the ability to accurately identify patients at risk and the development of preventative strategies remain unsolved issues.

Cerebral white matter lesions in patients with cirrhosis - causative for hepatic encephalopathy or bystanders?

Background & Aims: Focal white matter lesions mimicking microvascular lesions were connected to the development of hepatic encephalopathy (HE) in patients with cirrhosis. This study aims to assess the relationship between cerebrovascular risk factors and the prevalence and extent of these lesions in patients with cirrhosis, as well as their impact upon cognitive function.

Methods: 55 cirrhotic patients underwent neurological examination, psychometric testing and magnetic resonance imaging.

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt.

Background & Aims: Inflammation, collagen deposition and tissue remodelling are involved in the pathogenesis and complications of cirrhosis with portal hypertension. CXCL9 and other chemokines play an important role in these processes and have been associated with liver injury and complications of liver disease in humans. However, their predictive value in patients with cirrhosis and portal hypertension remains to be established.

Long-term outcome of liver transplantation in HCV/HIV coinfected haemophilia patients. A single centre study of 10 patients.

Unlabelled: The outcome and clinical features during long term follow-up of 10 haemophilia patients (haemophilia A n = 9, haemophilia B n = 1), who underwent successful orthotopic liver transplantation (OLT) due to hepatitis associated liver disease, are summarised.

Patients: Eight patients were HIV/HCV co-infected. Despite severe postoperative complications, which were not bleeding-associated, all patients survived OLT.

Central nervous system complications after liver transplantation: common but mostly transient phenomena.

Although central nervous system complications (CNSCs) are common after orthotopic liver transplantation (OLT), standardized prospective studies are still lacking. This prospective study was aimed at determining the incidence of CNSCs, describing their clinical presentations, and establishing predicting factors. One hundred thirty-six adult patients who underwent OLT at Hannover Medical School between December 2008 and June 2011 were included.

PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension.

Background: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection.

Methods: Fifty-eight patients (67% male, mean age: 36.

Regulatory CD4+ T cells modulate the interaction between NK cells and hepatic stellate cells by acting on either cell type.

Background & Aims: NK cells regulate liver fibrosis by killing activated hepatic stellate cells (HSCs) and are controlled themselves by immune cells and/or soluble factors. Here, we analysed if CD4(+) regulatory T cells (Tregs) modify the interaction between NK cells and HSCs.

Methods: The modification of NK cell activity against HSCs was studied in CD56(high)CD16(-) NK cells, using a flow cytometric CD107a degranulation assay and co-cultures with Tregs from healthy donors and patients with hepatitis C, respectively.

Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers.

Objectives: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes.

Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients.

Unlabelled: Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury.

A farnesoid X receptor polymorphism predisposes to spontaneous bacterial peritonitis.

Background: In mice, the farnesoid X receptor is involved in bacterial translocation, which can result in spontaneous bacterial peritonitis in patients with cirrhosis. We investigated if polymorphisms in the farnesoid X receptor gene influence the risk for spontaneous bacterial peritonitis.

Methods: Laboratory and clinical data of 293 cirrhotic patients with ascites and 226 healthy controls were prospectively collected.

The role of miRNA-34a as a prognostic biomarker for cirrhotic patients with portal hypertension receiving TIPS.

Background: Circulating miRNA-34a is increased in blood of patients with different liver diseases when compared to healthy controls. However, the origin of miRNA-34a and its possible relationship with hemodynamics and outcome in cirrhotic patients with portal hypertension is unknown. We analyzed the levels of miRNA-34a in cirrhotic patients with severe portal hypertension.

Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection.

The ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal treatment outcome in HIV co-infected individuals. Cohort study of 105 HIV-infected patients with AHC infection from five centres in two European countries was carried out. Choice of treatment with pegIFN-alfa alone (group 1; n = 36) or pegIFN-alfa and ribavirin (RBV) (group 2; n = 69) was at the discretion of the investigator.

Plasmid transfer of plasminogen K1-5 reduces subcutaneous hepatoma growth by affecting inflammatory factors.

There is evidence that plasminogen K1-5 (PlgK1-5) directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5) on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated.